Characterization of a human wearable ECG device for continuous in-cage data collection in non-rodents

Abstract

Wearables are commonly used in clinical diagnostic medicine and personal health tracking. However, their use to collect nonclinical endpoints is limited due design specification differences for human vs animal data (i.e. data format limitations, low sampling rates) and availability of nonclinical telemetry technologies both of which create a general “barrier to entry” to adopt and take advantage of clinical innovation in nonclinical studies. To determine the feasibility of using a human ECG wearable device (WRB) in nonclinical studies, we compared heart rate (HR) and ECG intervals between the wearable and implanted telemetry in canine and non-human primate (NHP). For this, n = 5 canine and n = 4 NHP, previously implanted with Stellar (STL) telemetry implants, were jacket-acclimated and then continuous ECGs (500 Hz) were collected 24 h prior and 24 h after oral administration of vehicle or dofetilide (canine: 0.003, 0.010, 0.030 mg/kg; NHP: 0.03, 0.06, 0.12 mg/kg) simultaneously from both devices. Data were extracted as 15-min means and reviewed qualitatively, by a Bland-Altman analysis (BA) to determine bias and 95 % limits of agreement (LOA) between measures, and by comparing the dofetilide-dependent average vehicle-adjusted QTci prolongation (DoubleDelta) from 1 to 3 h postdose. Generally, the 15 min averages over the 48 h period/dose levels were qualitatively consistent in magnitude and profile between the two measurement platforms. BA demonstrated that the measurements between the 2 devices were similar with bias (LOA) as follows: canine: HR +1 bpm (+8,-6); PR +0.4 ms (+9,-8); QRS +1 ms (+4,-2); QT +2 ms (+14,-11) and NHP: HR 0 bpm (+4,-4); PR +0.4 ms (+14,-13); QRS +2 ms (+8,-5); QT +7 ms (+29,-15). Dofetilide-dependent DoubleDelta QTci prolongation was similar between measurement platforms (STL vs. WRB): NHP: 0.03 mg/kg: +6 ms vs +7 ms, 0.06 mg/kg: +23 ms vs +20 ms, 0.12 mg/kg: +35 ms vs +41 ms; and canine: 0.003 mg/kg: +1 ms vs +3 ms, 0.010 mg/kg: +5 ms vs +6 ms, 0.030 mg/kg: +17 ms vs +17 ms. Overall, these studies demonstrate the feasibility of using alternative devices to collect in-cage ECG and provide initial data to investigate the broader potential of re-purposing clinical wearable devices to collect nonclinical safety pharmacology and toxicology endpoints.